The anterior paired lateral neuron normalizes odour-evoked activity in the Drosophila mushroom body calyx

Abstract

To identify and memorize discrete but similar environmental inputs, the brain needs to distinguish between subtle differences of activity patterns in defined neuronal populations. The Kenyon cells of the Drosophila adult mushroom body (MB) respond sparsely to complex olfactory input, a property that is thought to support stimuli discrimination in the MB. To understand how this property emerges, we investigated the role of the inhibitory anterior paired lateral neuron (APL) in the input circuit of the MB, the calyx. Within the calyx, presynaptic boutons of projection neurons (PNs) form large synaptic microglomeruli (MGs) with dendrites of postsynaptic Kenyon cells (KCs). Combining EM data analysis and in vivo calcium imaging, we show that APL, via inhibitory and reciprocal synapses targeting both PN boutons and KC dendrites, normalizes odour-evoked representations in MGs of the calyx. APL response scales with the PN input strength and is regionalized around PN input distribution. Our data indicate that the formation of a sparse code by the Kenyon cells requires APL-driven normalization of their MG postsynaptic responses. This work provides experimental insights on how inhibition shapes sensory information representation in a higher brain centre, thereby supporting stimuli discrimination and allowing for efficient associative memory formation.

Effects of stochastic coding on olfactory discrimination in flies and mice

“…The second model, called the multi-synapse model, incorporates recent work highlighting 2 complexities absent in the single synapse model. First, there are multiple synapses between APL and each KC [ 55 , 61 ]; moreover, the number of APL→KC synapses is correlated with the number of KC→APL synapses for each KC, and falls within a range (2 to 38 synapses, Fig 1 of [ 61 , 66 ]). Second, we included noise within KC processes that integrate inputs and push the membrane potential past the spike threshold [ 67 ].…”

“…The 2 models differ in their connectivity within the WTA circuit and helped us pinpoint the role of connectivity in generating the stochastic code. In the single synapse model, APL made a single synapse with each KC, where the strength of each synapse was equivalent to the synapse strength as per [ 55 , 61 ]. Or, equivalently, APL made multiple synapses with every KC, but, all synapses had the same noise (correlated noise).…”

Hacking brain development to test models of sensory coding

“…Kenyon cells activate an inhibitory neuron, APL, that feeds back on Kenyon cells to sparsen their firing (Lin et al, 2014). Recent work suggests that APL provides local feedback inhibition (Amin et al, 2020; Inada et al, 2017; Prisco et al, 2021). Our work here suggests that APL’s activity is determined by the proportion of active Kenyon cells, not the absolute number of active Kenyon cells.…”

Sleep benefits different stages of memory in Drosophila

“…A third group of dopaminergic neurons, PPL2, innervates the MB calyx and has been shown to shape olfactory responses in the KCs and modulate memory strength ( Mao and Davis, 2009 ; Boto et al, 2019 ). In addition to this complex circuitry, MB activity is modulated by other extrinsic neurons, some of which innervate widely the MB neuropile and whose activity is necessary for efficient memory acquisition, consolidation, and retrieval ( Yu et al, 2005 ; Liu and Davis, 2009 ; Cervantes-Sandoval and Davis, 2012 ; Lin et al, 2014 ; Amin et al, 2020 ; Baltruschat et al, 2021 ; Prisco et al, 2021 ).…”